This K24 proposal will provide protected time for Dr. Grijalva to deliver high-quality mentoring to post-doctoral and junior faculty investigators as well as to expand his studies of influenza transmission and disease prevention. Dr. Grijalva proposes a comprehensive and dedicated mentoring plan that will facilitate the effective transition of his mentees into independent academic careers. The application includes a detailed description of plans to augment Dr. Grijalva?s own training through acquisition of advanced skills in mentoring, and modelling of transmission of infectious diseases and causal inference. His current research projects are thematically linked through their focus on acute respiratory infections, especially influenza infections, with a strong emphasis on identification of modifiable risk factors to inform subsequent interventions. Influenza remains an important cause of morbidity and mortality worldwide. The primary strategy to attenuate the impact of influenza epidemics is vaccination, but vaccine effectiveness is suboptimal. Alternative methods to prevent the spread of influenza are needed. Little is known about the transmission of influenza in US households and communities in our modern lifestyle. Our understanding of influenza transmission is largely based on household studies that were done in the 1960?s and 1970?s. Diagnostic tests have changed, and current molecular and sequencing techniques allow accurate identification of influenza transmission. Similarly, contact patterns within households and communities have likely changed during the last decades, and widespread use of electronic devices may have further modified those dynamics. Understanding the contemporary drivers of influenza transmission within US households and communities is the foundation for preventative interventions. The NIAID strategic plan to prevent influenza infections and design a Universal influenza vaccine has identified modern studies of influenza transmission as an important research priority. Although a large proportion of influenza infections are acquired at home, the role of household environment, contact patterns, and disease severity on influenza transmission have not been well studied. Contemporary household case-ascertained studies are efficient designs to quantify transmission parameters and to study the role of these and other novel modifiable factors. The research aims are: 1) Test the hypothesis that modifiable factors, including household temperature, relative humidity, and within-household social interactions are independently associated with the risk of influenza transmission in households; 2) To provide a comprehensive assessment of the use and effectiveness of antivirals in the prevention of influenza transmission in households; 3) Test the hypothesis that the disease severity in the index case (first patient infected in the household), and the household exposure intensity and duration modify the risk of influenza transmission in households. These studies will inform the design and evaluation of new prevention strategies, and will provide extensive opportunities for mentoring junior investigators in patient-oriented research in influenza infections, transmission and prevention.